Welding fume exposure and associated inflammatory and hyperplastic changes in the lungs of tumor susceptible a/j mice

Toxicol Pathol. 2006;34(4):364-72. doi: 10.1080/01926230600815122.

Abstract

It has been suggested that welding fume (WF) exposure increases lung cancer risk in welders. Epidemiology studies have failed to conclude that WF alone causes lung cancer and animal studies are lacking. We examined the course of inflammation, damage, and repair in the lungs of A/J mice, a lung tumor susceptible strain, caused by stainless steel WF. Mice were exposed by pharyngeal aspiration to 40 mg/kg of WF, silica, or saline. Bronchoalveolar lavage (BAL) was performed 24 hours, 1 and 16 weeks to assess lung injury and inflammation and histopathology was done 1, 8, 16, 24, and 48 weeks postexposure. Both exposures increased inflammatory cells, lactate dehydrogenase and albumin at 24 hr and 1 week. At 16 weeks, these parameters remained elevated in silica-exposed but not WF-exposed mice. Histopathologic evaluation at 1 week indicated that WF induced bronchiolar epithelial hyperplasia with associated cellular atypia, alveolar bronchiolo-alveolar hyperplasia (BAH) in peribronchiolar alveoli, and peribronchiolar lymphogranulomatous inflammation. Persistent changes included foci of histiocytic inflammation, fibrosis, atypical bronchiolar epithelial cells, and bronchiolar BAH. The principle changes in silica-exposed mice were histiocytic and suppurative inflammation, fibrosis, and alveolar BAH. Our findings that WF causes persistent bronchiolar and peribronchiolar epithelial changes, suggest a need for studies of bronchiolar changes after WF exposure.

MeSH terms

  • Animals
  • Bronchoalveolar Lavage Fluid / chemistry
  • Bronchoalveolar Lavage Fluid / cytology
  • Gases / chemistry
  • Gases / toxicity
  • Genetic Predisposition to Disease*
  • Hyperplasia / chemically induced
  • Hyperplasia / pathology
  • Inhalation Exposure*
  • Lung / drug effects*
  • Lung / pathology
  • Lung Neoplasms / chemically induced
  • Lung Neoplasms / genetics*
  • Lung Neoplasms / pathology
  • Male
  • Mice
  • Mice, Inbred A
  • Particle Size
  • Pulmonary Fibrosis / chemically induced
  • Pulmonary Fibrosis / pathology
  • Silicon Dioxide / toxicity
  • Specific Pathogen-Free Organisms
  • Stainless Steel / toxicity
  • Time Factors
  • Welding*

Substances

  • Gases
  • Stainless Steel
  • Silicon Dioxide